The present invention relates to a field-effect device for the detection of small quantities of electric charge, such as those generated in bio-molecular processes, bound in the vicinity of its surface.
In the scientific literature there are known devices which exploit the measurement of the electric charge for particular applications by means of the use of a single device such as an ISFET. ISFET represents an evolution of the MOS transistor and allows the measurement of the pH of a solution by measuring the electric charge carried by the ions dissolved in the solution, bound to particular “binding sites” on the surface of the silicon. Devices for detecting small quantities of electric charge are utilised for recognition of the hybridisation process of a single strand of DNA. For this purpose the most widely used technique at the moment, however, involves the use of a micro-array of optically read fluorescent markers; single strand portions of DNA are fixed to a substrate of silicon dioxide (glass), and the complementary strand which can be expected to be found in an analysis sample is labelled with fluorescent molecules (markers); the hybridisation phase then proceeds in which the re-combination of the complete double helix is encouraged if the gene or the portion of DNA sought is located in the analysis sample. If the sample contains the gene sought, this strand binds itself to that fixed on the surface of the glass, thereby “gluing” the fluorescent marker onto a particular portion of the substrate, and the occurrence of hybridisation (and therefore the presence of the gene) can then be verified by means of an optical analysis of the surface. This method involves the use of costly equipment (above all optical systems) which is large and not transportable.
In recent years scientific research has made considerable efforts to achieve direct detection of the DNA hybridisation process by means of a measurement of electronic type. Plasma techniques have now been proposed, and techniques based on the use of the MEMS structures (Micro-Electrical-Mechanical-Systems) which, for example, make use of the so-called cantilevers and micro-balances. Other methods are based on the use of micro-electrodes, or on capacitive effects, others still utilise field effect transistors (FET).
International patent application WO-03/073088 describes a FET sensor device having a single floating gate.
U.S. patent application US-2003/152929 describes an elaborate system for detecting the hybridisation of individual portions of a DNA strand by means of charge measurements which are effected by reference to a cell containing known recombinant DNA (double helix).
International patent application WO-03/014722 describes the use of a field effect transistor for the detection of hybridisation of single strands of DNA.
One object of the present invention is to provide an improved device for the detection of very small quantities of electrical charge, which can be formed in a relatively simple and economic matter and which allows a direct reading of a charge variation without the necessity for external apparatus.
This and other objects are achieved according to the invention with a device comprising a chip in which is integrated in a MOS device having a floating gate, a first portion of which extends in facing relation to a recess formed in a surface of the chip and is covered by an interface layer which is accessible from outside the chip and is able to retain an electrical charge to be measured, applied to it; a second portion of the gate of the said MOS device being coupled to a control electrode of the chip by means of a capacitor of predetermined value within the chip.
Conveniently, the chip of the device for detecting small quantities of electrical charge according to the invention can be formed with a standard CMOS process. This allows production at low cost and the possibility of being able to exploit continuous improvements of CMOS technology in a direct and immediate manner, in particular in terms of scale of integration and availability of processor modules and CAD products for design purposes which have been already developed.
Further characteristics and advantages of the invention will become apparent from the following detailed description, given purely by way of non-limitative example, with reference to the attached drawings, in which: